This invention relates to trioxolane and diperoxide compounds. More particularly, it relates to formation of these compounds from unsaturated hydrocarbons and pharmaceutical preparations including these compounds for treating or preventing medical conditions. It also relates to methods of treating or preventing medical conditions using the trioxolane and diperoxide compounds.
A trioxolane compound is herein defined as a compound of the general structure: ##STR1## wherein R and R' represent the same or different organic moieties. The indicated carbons may also have additional organic moiety branches.
A diperoxide compound is herein defined as a compound of the general structure: ##STR2## wherein R and R' represent the same or different organic moieties. The indicated carbons may also have additional organic moiety branches.
Procedures for ozonating oil-soluble compounds are known in the art, being disclosed, for example, in U.S. Pat. No. 925,590 to Neel, U.S. Pat. No. 2,083,572 to McKee, and U.S. Pat. No. 4,451,480 to De Villez. However, not all ozonation reactions result in the production of trioxolane and diperoxide compounds. The production of such compounds from unsaturated hydrocarbons is disclosed in Murray et al., "Ozonolysis: Formation of Cross Diperoxides" and Criegee et al, "Fragmentation of Ozonides by Solvents," both in Ozone Reactions with Organic Compounds, Advances in Chemistry Series 112, American Chemical Society, Washington, D.C. (1972). The disclosures of these two references are incorporated herein in their entirety by reference thereto.
Ozonation of olefins is generally recognized in terms of a mechanism postulated by Criegee, supra. This mechanism provides that ozone reacts with an unsaturated bond to form an initial, unstable primary ozonide (R--C--O.sub.3 --C--R'). This primary ozonide readily decomposes to form a zwitterion and a carbonyl fragment. These fragments can then combine to give a trioxolane compound. Under other conditions, the zwitterion may dimerize to form a diperoxide derivative.
The prior art discloses that some particular types of ozonated chemical compositions have certain pharmacological activities. However, as far as Applicants can ascertain, none of these compositions appear to have been prepared in a manner likely to result in the formation of substantial quantities of diperoxide or trioxolane compounds.
In U.S. Pat. No. 925,590, Neel discloses the use of ozonated hydrocarbons for inhalation therapy, because it was believed to have a therapeutic effect for consumption and asthma. Even had the ozonation system of Neel resulted in the formation of substantial quantities of diperoxide or trioxolane compounds, such compounds have very low vapor pressures. Thus, only insubstantial quantities of diperoxide or trioxolane compounds would be expected to be found in vapor.
Knox, U.S. Pat. No. 1,210,949 discloses ozonation of castor oil in order to produce a laxative. Ozonation of the oil was believed to reduce its toxicity and create a germicidal effect. In order to produce substantial quantities of diperoxide or trioxolane compounds using the method disclosed by Knox, temperatures approaching -50.degree. C. using a very dilute solution would be required.
Johnson, U.S. Pat. No. 2,356,062 discloses the use of ozonides of glycerine trioleates for external application, because it was believed that those particular triglycerides had a germicidal, fungicidal, and deodorizing effect. The methods of Johnson, for reasons described above in connection with the patent to Knox, are also not believed to result in the production of significant quantities of diperoxide or trioxolane compounds.
DeVillez, U.S. Pat. Nos. 4,451,480 and 4,591,602, discloses use of ozonides of certain fatty acids, including olive oil, sesame oil, jojoba oil, castor oil, and peanut oil, for external use as antimicrobial agents, particularly in the treatment of acne. It is believed that at least some of these compounds cause unacceptable skin irritation. DeVillez dicloses ozonation at 35.degree.-65.degree. C., a temperature at which diperoxides and trioxolanes are not expected to be formed in substantial quantities.
Accordingly, so far as can be determined, none of the medical uses of ozonated compounds described in the prior art have ever made use of substantial quantities of trioxolane or diperoxide compounds. Moreover, none of the prior art ozonated compounds appears to have ever been commercialized for medical applications. Presumably, this lack of commercialization is due to unacceptable side-effects, toxicity, difficulties in storage, or minimal effectiveness. Many of these various compositions decompose on standing.
Immunomodulation offers an opportunity to treat a variety of medical conditions. For example, both infections and neoplasms can be treated by increasing the immune response thereto. Some allergic reactions and other auto-immune responses can also be treated through immunomodulation. However, there are few effective immunomodulatory therapies known; and many of the known immunomodulatory therapies produce untoward side effects. Thus, there is a need for safe and effective immunomodulatory treatment.
At any one time, it is estimated that 1/3 of all women are suffering from bacterial or fungal vaginal infection. The only presently available treatments are time consuming and the medications used are irritating to mucous membranes. Thus, there is a need for a relatively non-irritating, safe, and effective composition for treatment of these infections.
Genital herpes lesions and Herpes simplex lesions are notoriously resistant to treatment. These viral infections inflict a significant percentage of the population, and there is, at present, no known cure. Thus, a need exists for compositions that can treat herpes lesions in at least a palliative manner to minimize the discomfort suffered by those suffering from these diseases.
Chicken pox (Herpes zoster) is a common childhood disease, for which no vaccine is currently known. Lesions of chicken pox cause itching, and may lead to permanent disfigurement, if scratched. Since the disease strikes mainly children, who are unable to resist scratching, the need exists for compositions that can anti-pruritically treat chicken pox lesions to minimize disfigurement caused by the disease.
External fungal infections, such as athletes foot and onychomycosis (fungal infections of the nails), afflict a large portion of the human population. Similar fungal infections afflict a large percentage of the animal population. Current treatments for external fungal infections are irritating to sensitive individuals, and not always effective. In addition, onychomycosis is difficult to treat, and its incidence appears to be on the rise with the advent of acrylic and other adhesively-mounted artificial nails. Therefore, a need exists for a relatively non-irritating, effective treatment for these infections.
Indolent neoplasms of the skin, such as warts and moles, also afflict a large portion of the human and animal population. Current over-the-counter medications are not always effective, and the only effective therapy in some instances is to have the neoplasms frozen or burned off, necessitating a doctor's visit. Thus, a need exists for a treatment which is effective, and which can be applied by the patient or owner of the afflicted animal.
Steroidal medications are currently in widespread use to relieve the discomforts of bee stings, insect bites, and other dermatoses, such as those caused by psoriasis, poison oak, or poison ivy. While these medications are sometimes effective, their long term use can result in side effects, including thinning of the skin, sleeplessness, physical deformation, improper fat deposition, dependency, and others. Thus, there is a need for an effective alternative medication for these ailments.
Symptoms of sunburn can range from mild discomfort to severe burns. This condition occasionally affects virtually the entire population. Current treatments do little more than mask the pain associated with this condition. Products which prevent sunburn, when applied prior to exposure, are currently available. However, there is no product currently available which prevents sunburn symptoms or alleviates the severity of sunburn when applied after exposure to the sun. Many people carelessly or inadvertently expose themselves to the sun without using protective sunscreens. Thus, a need exists for a product that can prevent sunburn after exposure to the sun.
In the treatment of severe burns, prevention of dehydration and infection in the burned patient are major concerns. Currently used therapies for severe burns which address these concerns are often irritating to sensitive, burned tissues. Thus, there is a need for a method of treating burns that is non-irritating, yet still effective against both dehydration and infection.
Many adolescents and young adults suffer from acne. Many compounds are currently available to treat acne, with variable effectiveness. The most effective compositions currently known to treat acne use active oxygen to kill the bacteria which are, in part, responsible for the condition. These include benzoyl peroxide. However, these compositions are sometimes irritating, do not always deliver enough oxygen for optimal effectiveness, and can cause drying of the skin. Thus, a need exists for a non-desiccating, effective, and non-irritating treatment for acne.
Sexually transmitted diseases (STDs), including herpes, syphilis, gonorrhea and AIDS, are endemic in today's society. Condoms are currently the most effective means of preventing the transmission of these diseases. However, condoms are not 100% effective. A need, therefore, exists for preparations which increase the effectiveness of condoms in preventing the transmission of STDs.
Both topical and systemic Leishmaniasis are widespread throughout the tropical areas of the world. Presently, at least 4,000,000 people are know to be infected with a parasite which causes one of these conditions. No totally effective therapies are known. Accordingly, a clear need is evident for an effective treatment or therapy for these diseases.